There is a variety of medical procedures that require light or irradiated energy to be administered to a patient within the body. One example is that of therapeutic methods that use a light activated compound to selectively kill target cells in a patient, termed photoactivated chemotherapy. Other examples include optical diagnostic methods, hypothermia treatment and biostimulation. In photoactivated chemotherapeutic methods, a light-sensitive drug is injected into a patient and a targeted light source is used to selectively activate the light-sensitive drug. When activated by light of a proper wavelength, the light-sensitive drug produces a cytotoxic agent that mediates the destruction of the surrounding cells or tissue.
The main application of photoactivated therapy, such as PDT, is for the destruction of malignant cell masses. Photoactivated therapy has been used effectively in the treatment of a variety of human tumors and precancerous conditions including basal and squamous cells, skin cancers, breast cancer, metastatic to skin, brain tumors, head and neck, stomach, and female genital tract malignancy, cancers and precancerous conditions of the esophagus such as Barrett's esophagus. A review of the history and progress of photoactivated therapy is provided by Marcus, S. Photodynamic Therapy of Human Cancer: Clinical Status, Potential, and Needs. In Gomer, C. J. (ed.); "Future Directions and Applications in Photodynamic Therapy." Bellingham, W. A. SPIE Optical Engineering Press (1990) pp 5-56 and specific applications of PDT are provided by Overholt et al., Sem. Surg. Oncol. 11:1-5 (1995).
One area of focus in the development of phototherapeutic methods and apparatus is the development of targeted light sources that provide uniform illumination to a given treatment area.
Allardice et al. Gastrointestinal Endoscopy 35:548-551 (1989) and Rowland et al. PCT application WO 90/00914, disclose one type of light delivery system designed for use with PDT. The disclosed system involves a flexible tube comprising a dilator and a transparent treatment window that defines a treatment area by using opaque end-caps made of stainless steel. A fiber optic element that is connected to a laser and ends in a diffusing tip is used in combination with the dilator to deliver light to a tissue source. Allardice et al. discloses that the advantages of this apparatus over the use of balloon-type catheter reside in providing a more uniform distribution of light.
Nseyo et al. Urology 36:398-402 (1990) and Lundahl, U.S. Pat. Nos. 4,998,930 and 5,125,925, disclose a balloon catheter device for providing uniform irradiation to the inner walls of hollow organs. The device is based on a balloon catheter design and includes a balloon at one end of the apparatus and an optical fiber ending in a diffusion tip that is inserted into the lumen of the balloon through the catheter. The use of the catheter's centering tube was disclosed as providing a more uniform distribution of the laser light by centering the optical fiber in the inflated balloon. The catheter devices disclosed in these references further incorporate optical sensing fibers in the balloon wall to provide means for measuring illumination. However, there is no disclosure about the use of specific coating materials on the balloon to improve light uniformity or the use of a long diffusion tip that is longer than a delineated treatment window.
Panjehpour et al. Lasers and Surgery in Medicine 12:631-638 (1992) discloses the use of a centering balloon catheter to improve esophageal photodynamic therapy. Panjehpour discloses a cylindrical balloon catheter into which a fiber optic probe ending in a light diffuser is inserted. The cylindrical balloon containing the catheter is transparent and is not modified with a reflective coating to improve the diffusion of light within the balloon or to define a treatment window
Overholt et al. Lasers and Surgery in Medicine 14:27-33 (1994) discloses modified forms of the balloon catheter device described by Panjehpour. The cylindrical balloon catheter was modified by coating both ends of the balloon with a black opaque coating to define a 360 degree treatment window. Overholt additionally describes a modified balloon in which one-half of the circumference of the treatment window is rendered opaque to light using the black coating material. This configuration provides a 180.degree. treatment window. The black color guard used in the balloon to define the target window was not a reflective material and did not increase the uniformity of the light passing through the treatment window.
Rowland et al. PCT application WO 90/00420, discloses a light-delivery system for irradiating a surface. The device comprises a hemispherical shell whose inside is entirely coated with a diffuse reflector and a light source that is mounted within the shell. The light source may contain a diffusing source at the tip allowing diffusion of light within the reflective shell.
Spears, U.S. Pat. No. 5,344,419, discloses apparatuses and methods for making laser-balloon catheters. Spears utilizes a process that etches an end of a fiber optic cable to provide a diffusion tip on the optical cable. The optical cable containing the etched tip is secured within a central channel of a balloon catheter using a coating of adhesive containing microballoons. The position of the tip within the central channel and the microballoons contained in the adhesive provide increased efficiency in diffusing the laser radiation in a cylindrical pattern, providing a more uniform illumination at the target site.
Beyer, et al. U.S. Pat. No. 5,354,293 discloses a balloon catheter apparatus for delivering light for use in PDT. The balloon catheter device disclosed employs a conical tipped fiber optic cable to provide means of deflecting a light beam radially outward through a transparent portion of an inflated catheter.
In summary, there have been numerous devices that have been developed for use in PDT that employ a balloon catheter to support a light source in an ideal central point within a target area that is to be illuminated (Spears, Overholt, Beyer, Lundahl and Allardice). The main benefits of using a centering type balloon are that 1) the clinician does not have to hold the fiber optic in the central location, this is done automatically by the balloon catheter, 2) the light dose is more uniform across the entire treatment are than would be the case of light delivered by a fiber optic that is held central to the treatment volume without the aid of a balloon (while this is true with existing designs of balloon catheters, it is herein demonstrated that the uniformity can be significantly improved), 3) the treatment field is kept clean of contaminants e.g. blood, urine that might absorb the light and so effect the final PDT result, and 4) the overall treatment procedure can be considerably shortened as it is simpler setting up the fiber optic and getting the light dose correct. However, the disadvantage of using current cylindrical centering balloons with existing fiber optic diffusers is the inability to obtain uniform light being transmitted through the balloon to the target site.
Although each of the above disclosures provides means for providing light to a target site, there is no suggestion to use a reflective coating at the ends of a balloon catheter as a means of increasing uniformity in the distribution of the transmitted light. In addition, none of the devices employs a diffusing tip at the end of the fiber optic cable that is longer than the treatment window. These two features are present, alone or in combination, in the apparatus of the present invention and provides improved balloon catheter devices that more uniformly and efficiently distribute light over a treatment area.